by Dr. J. Nathan

KETOGENIC THERAPY AND AUTISM

Autism Spectrum Disorder(ASD) Sinna, 3 yrs old was a cheerful boy. When Sinna with his parents visited his paediatrician for a regular check-up, Paediatrician asked the normal development question which his parents could easily answer. After a year, his parents found his behaviour hard to understand. He didn’t make eye contact and he barely spoke, He didn’t play with other children, or with toys, in the way they expected. Without vital communication skills Sinna had no way to express his needs and wants and would often become frustrated or distressed. His parents could see that he was struggling. “He used to bang his head against a wall or the floor – he was so frustrated”. These symptom could be Autism traits, which Sinna’s parent soon realised and took him to a paediatrician for evaluation.Does your child have any of the following Autism traits:- • Absent/poor eye contact • Repetitive language • Repetitive gesture/actions • Does not play or mix with peer group • Delayed language development • Impaired social interaction • Poor verbal and non-verbal communication • Stereotypies in behaviour- repetitive, purposeless actions. • Associated sensory processing difficulties:- over responsiveness to sensations like touch, light, sound etc. Impairments range from mild to severe, Each area of development may be affected to a different degree in the same child. So let us first understand what Autism is and how we can tackle it.

Autism Spectrum Disorder(ASD) is a Complex Neuro-developmental Disorder marked by following traits:

Incidence and Aetiology of ASD:- ● The number of children diagnosed with autism spectrum disorder (ASD) has increased significantly over the last few decades. ● Incidence in India 1:60 to 1:100 ● Male preponderance (M/F = 4:1) ● No clear aetiology and therefore NO cure for autism. ● It has been suggested that nutritional factors play a major role. ● Significantly lower levels of various nutrients have been observed in autistic children including low levels of zinc, selenium, vitamin D and omega-3 fatty acids (Elder, 2008).Diagnosis of ASD is based on:- ● History ● Neuropsychological tests ● Diagnosis o Reliable diagnosis as early as 2 years o Possible even as early as 6 months o Average age at diagnosis is still 4 years in developed countries and in India ● Early intervention is always the key ● Dietary Therapy ● Occupational Therapy ● Speech Therapy ● Behavioural TherapyASD – Causes and Target systems:-

ASD interplay between genes and environment Genes – Several hundred gene mutations have been foundEnvironment:- o Parental age o Adverse metabolic conditions o Maternal illness during pregnancy o Birth complications o Drug and toxin exposure during early brain developmentGI system & Autism ● Balance of the gut is disturbed i.e. diarrhoea and bloating ● Leads to overgrowth of microbes causing inflammation. ● Leads to swelling that puts pressure on all the cells in the digestive tract that allows intra intestinal material to escape known as ‘leaky gut’. ● Harmful or undesirable microbes migrate to the small intestine where they compete for nutrients and disrupt digestion by damaging enzymes needed to break down food.

Potential relationships between the microbiota and ASD (the gut-brain axis). The production of metabolites, such as SCFAs (Short chain fatty acids) and toxin metabolites, by certain microbiota (e.g., Lactobacillus) that can cross the “leaky gut” to affect brain function. Some microbiota can produce neuroactive compounds (e.g.,5-HT and GABA) that cross the “leaky gut” and influence brain function and induce abnormal behaviors. These neuroactive compounds can directly influence the HPA axis and increase circulating levels of cortisol. Metabolites, certain microbiota and neuroactive compounds can activate enteric neurons and affect brain function through the vagus nerve. Some microbiota and metabolites can activate gut immune cells, which can release cytokines into circulation. 4-EPS, 4-ethylphenyl sulfate; 5-HT, serotonin; HPA, hypothalamic–pituitary–adrenal; SCFAs, short-chain fatty acids; BBB, blood-brain barrier; 5-HT, 5-hydroxytryptamine; ENS, enteric nervous system; GABA, g-aminobutyric acid; DA, dopamine.( Li et al. 2017) Leaky gut is common in most of the neurological disorder. So we will study in depth about this on our next post. So stay tuned with us. Is there a specific medication to treat ASD? Answer is ‘NO’ So what is the other option, Its DIET. Specialized diets used in autism Statistics show that at least 40% of children with autism have been placed on a specialized diet at some point in their lives in an effort to improve the symptoms of autism. The most commonly used specialized diets are: ● Gluten-Free/Casein-Free Diet ● Organic Diet/Limiting Processed Foods ● Yeast free diet ● Restriction of food allergens ● Probiotics, and dietary supplementation with vitamins A, C, B6, folic acid , B12, minerals like magnesium and omega-3 fatty acids ● Ketogenic Diet (KD)

So we will study in detail about 3 of the above highlighted diets which are commonly used:-

GLUTEN FREE CASEIN FREE DIET It has been suggested that peptides from gluten and casein may have a role in the origins of autism and that the physiology and psychology of autism might be explained by excessive opioid activity linked to these peptides.( Ly et al. 2017) Only three papers reporting on two randomised control trial were identified, two small scale trials the first with ten participants in each arm of the trial and the second with fifteen participants recruited into the trial. (Valenti, S et al. 2017) The results for the first study indicated that a combined gluten and casein free diet reduced autistic traits and the second study showed no significant difference in outcome measures between the diet group and the control group. (Whitehouse, A. J.et al, 2013) So, there is a lack of evidence to support the use of gluten and/or casein free diet as an effective intervention for persons with autism and also a lack of research on potential harms and drawbacks of such diets. (Carlon, S. et al, 2013)

PROBIOTICS Gastrointestinal (GI) dysfunction has been reported in a substantial number of children with autism spectrum disorders (ASD). Activation of the mucosal immune response and the presence of abnormal gut microbiota are repeatedly observed in these children. (K. Horvath et al. 2002). In children with ASD, the presence of GI dysfunction is often associated with increased irritability, tantrums, aggressive behaviour, and sleep disturbances. (C. A. Molloy et al. 2003) A study reported that modulating gut bacteria with short-term antibiotic treatment can lead to temporary improvement in behavioral symptoms in some individuals with ASD. (R. N. Nikolov et al. 2009) Probiotics can influence microbiota composition and intestinal barrier function and alter mucosal immune responses. The administration of probiotic bacteria to address changes in the microbiota might, therefore, be a useful novel therapeutic tool with which to restore normal gut microbiota, reduce inflammation, restore epithelial barrier function, and potentially ameliorate behavioural symptoms associated with some children with ASD. (H. Gill and J. Prasad, 2008)

Ketogenic Diet (KD) and ASD ● Individuals with epilepsy often have behavioural problems and deficits in attention and cognitive functioning. ● KD has been found to effect improvements in these domains. Hence it is also postulated that KD may act as a mood stabilizer. ● Recent studies have also demonstrated its use for autism and mood disorders. ● The mechanism of action of KD is manifold. ● Ketogenic diet (KD) produces o high ketones o low glucose o increase in PUFAs ● Ketogenic diet extremely limits sweet and starchy processed foods. o This deprives certain gut bacteria of the food they need and may be a way to help restore balance in the microbiome. o Masino et al (2013) , found that certain biological compounds increase in the brain while on the ketogenic diet. She hypothesized that a compound called adenosine may be key to the diet’s effects and may also be helpful in alleviating symptoms of autism. Specific Carbohydrates diet & Autism:- o Carbohydrates, that are not completely digested, stay in the digestive tract and become “food” for unhealthy microbes o As the microbes digest the leftover carbohydrates, the fermentation damages the digestive tract. o These cause digestive symptoms and nutrient deficiencies. o Easily digested carbohydrates like vegetables, fruits along with meat & healthy fats should be consumed We combine gluten- casein free diet and probiotics with ketogenic diet.

AUTISM CASE REPORT ( AT OUR CENTER)- HISTORY ● Name: SB ● Age: 14 years old ● Diagnosed with epilepsy when he was 1.5 years of age. ● He had atonic jerks on an average 2-3 per day ● He was irritable and would get aggressive especially with his mother ● Prone to irrelevant talking and not inclined towards socializingKD THERAPY ● The patient visited us in January 2015 and was started on ketogenic diet. ● Calories: 850 Kcal (75 % RDA) ● Keto ratio: 2.5:1 (2.5 gms fat to 1 gm protein + carbohydrate) ● The calories & ratio was fine-tuned on monthly basis to maintain 4+ ketones ● MCT oil therapy was also started with a dose of 5 ml per meal & gradually increased as per his tolerance IMPROVEMENT ● His jerks have reduced to 2 per month and it mostly occurs in sleep ● He is now more open to change in general ● There is willingness to meet people and interact with them ● Emotionally tries to connect. Protective about his things ● His irritability has reduced considerably ● He has yet be prepared for a ‘no’- gets angry for direct instructionPRE & POST CARS SCORES

CARS interpretation He can relate better to people, there is improved communication and his emotional responsivity has increased. SB’s parents reported a decrease in his overall features of autism.